Safety and Efficacy of Anti-CD123 Chimeric Antigen Receptor-Modified Autologous T Cells (CART123) in Patients with Relapsed/Refractory CD123+ Hematologic Malignancies: a Dose Escalation, Open-Label, Phase I Study
Adult patients with refractory or relapsed CD123+ hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or blastic plasmocytoid dentritic cell neoplasm will be recruited in the trial. CART123 cells will be manufatured from blood of each patient. During the production of CAR123 cells, patients may receive appropriate bridging therapy. After cells are produced, participants will undergo a single course of lymphodepleting chemotherapy and receive a single dose of CAR123 T cells. The trial will establish the recommended dose for further studies, either the Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD). Patients must be eligible for hematopoietic stem cell transplantation in order to participate in the trial.
• Patients with AML, MDS-IB2, BPDCN or ALL positive for CD123 antigen, who meet one of disease specific criteria below:
• a) Patients with AML will be eligible if they meet one of the following criteria:
• i) Patient with refractory AML defined as failure to achieve CR or CRi after at least 2 cycles of induction chemotherapy or 1 cycle of high dose salvage regimen or 4 cycles of venetoclax with azacytidine OR
• ii) Second or subsequent relapse of AML OR
• iii) Relapse after allogeneic HSCT.
• b) Patients with ALL will be eligible if they meet one of following criteria:
• i) disease refractory to or relapsed after CAR-19 cell therapy OR
• ii) CD19 negative relapse ineligible for treatment with TKI inhibitors and inotuzumab ozogamicin.
• c) Patients with BPDCN will be eligible if they meet following criteria:
• i) Refractory or relapsing after chemotherapy with or without allogeneic stem cell transplantation.
• d) Patients with MDS-IB2 will be eligible if they meet one of following criteria:
• i) Disease refractory to at least four cycles of azacytidine or progression on azacytidine-based therapy OR
• ii) Disease refractory to induction chemotherapy OR
• iii) Relapse after haematopoietic stem cell transplantation.
• CD123 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry.
• Age between 18 and 70 years.
• Patient has a suitable donor for allogeneic hematopoietic stem cell transplantation. Workup and clearance of the donor must be completed before IMP administration.
• Patient able to understand and sign informed consent.
• Women of child-bearing potential: negative pregnancy test at enrolment (PSV) and at Visit 1.
• Patient for whom there are no standard-of-care treatments available or such treatment options have been exhausted.